宫颈鳞状上皮癌变过程中IKKβ表达及意义

目的通过研究慢性宫颈炎、宫颈上皮内瘤样病变和宫颈鳞癌中IKKβ的表达情况,初步探讨IKKβ在宫颈鳞状上皮癌变过程中的作用。方法选取中国医科大学附属盛京医院病理科2010-2015年的100例宫颈组织石蜡标本。所有标本都由两名病理科医师独立诊断并复核确诊,按病理类型分为4组:慢性宫颈炎组(20例),CINⅠ组(20例),CINⅡ~Ⅲ组(20例),宫颈鳞癌组(40例)。采用免疫组织化SP法检测IKKβ在慢性宫颈炎、宫颈上皮内瘤样病变和宫颈鳞癌中的表达,比较各组间IKKβ的平均光密度值。结果 IKKβ阳性表达主要定位于宫颈鳞状上皮细胞的细胞浆,少数可见胞核着色。随着宫颈病变的进展,IKKβ的平均光密度值逐渐增加。宫颈鳞癌组的IKKβ平均光密度值较宫颈炎组、CINⅠ组和CINⅡ~Ⅲ组均显著升高(P<0.01)、而宫颈炎组和CINⅠ组的平均光密度值比较,差异无统计学意义(P>0.05)。结论本研究运用免疫组织化学方法检测出人类宫颈鳞状上皮癌变过程中各病变阶段鳞状上皮细胞胞浆中均有IKKβ的表达;且随着宫颈病变的进展,IKKβ的平均光密度值逐渐增加,在宫颈鳞癌组织中呈高表达,表明IKKβ的过度表达在宫颈鳞状上皮癌变道程中起促进作用。     

Inhibitors of TLR-4, NF-κB,and SAPK/JNK signaling reduce the toxic effect of lipopolysaccharide on RAW 264.7 cells

The present study was designed to examine and compare the effects of three suppressors on the cytokine response in tandem with examining: the synthesis of inducible forms of heat shock proteins; HSP72 and HSP90α; activities of NF-κB and SAPK/JNK signaling pathways; and TLR4 expression. Pre-treatment with inhibitors offers promise as protective means to lower the activity of these cascades, thereby circumventing the formation of excessive amounts of pro-inflammatory molecules. Three inhibitors of TLR4, SAPK/JNK, and NF-κB signaling, namely CLI-095, SP600125, and IKK Inhibitor XII, respectively, were added to cultured RAW 264.7 macrophages before the Escherichia coli lipopolysaccharide (LPS) application. Treatments of RAW 264.7 cells with each of the inhibitors resulted in a reduced response to LPS as was visualized by a decrease of TNF-α, IL-1, and IFN-γ production. In addition, inhibitors of the NF-κB and SAPK/JNK signaling reduced IL-6 production in LPS-treated cells, whereas the IKK inhibitor XII also decreased IL-10 production. Further, the NO production in LPS-stimulated macrophages was significantly reduced following application of CLI-095 or IKK inhibitor XII. The results also showed that the inhibitors suppressed TLR4 production and decreased phosphorylation of NF-κB and SAPK/JNK proteins, thereby preventing the activation NF-κB and SAPK/JNK signaling pathways in LPS-activated cells. In addition, the production of inducible heat shock proteins, HSP72 and HSP90-α, was reduced in LPS-stimulated RAW 264.7 cells pre-treated with inhibitors. These results suggest that inhibitors CLI-095, SP600125, and IKK inhibitor XII demonstrate potential effectiveness in the reduction of the inflammatory response by mechanisms involving both the cellular defense system and cellular signaling. In conclusion, suppressor of NF-κB cascade, IKK inhibitor XII, seems to be the most effective anti-toxic agent among studied inhibitors.     

rhGH对Jurkat细胞中NF-κB活性的影响

目的:探讨重组人生长激素(rhGH)对Jurkat细胞核因子-κB(NF-κB)信号通路活化的影响.方法:(1)将含荧光素酶报告基因的质粒pNF-κB-luc转染入T淋巴细胞系-Jurkat E6-1细胞中,在培养液中加入梯度浓度rhGH.(2)用梯度浓度rhGH直接刺激Jurkat细胞,然后用RT-PCR方法检测IκBα、IKK1 mRNA表达情况.结果:各浓度rhGH对转染pNF-κB-luc的Jurkat细胞中荧光素酶表达有促进作用,而对IκBα、IKK1 mRNA表达无显著影响.结论:rhGH对PHA活化的T细胞NF-κB的活化有促进作用,而对与NF-κB活化相关的IκBα和IKK1的mRNA表达无显著影响.     

I_κB kinase-beta inhibitor attenuates hepatic fibrosis in mice

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice rec...     

Blocking of PI3K/AKT induces apoptosis by its effect on NF-κB activity in gastric carcinoma cell line SGC7901

NF-κB plays an important role in many aspects of tumorigenesis and tumor progression by its antiapoptosis effect. Hence, NF-κB has been regarded as a therapeutic target in cancer, because inhibition of NF-κB not only induces enhancing apoptosis but also causes increasing sensitivity to radiation or chemotherapy in several tumor cells. The activation of NF-κB is presumed to be associated with PI3K/Akt signal pathway in gastric carcinoma, but the underlying molecular mechanism remains unclear. Our work demonstrates that blocking PI3K/Akt by LY294002 inhibits the NF-κB activity with significantly increased apoptosis in gastric cancer cell. Furthermore, when the cells were pretreated with IKK siRNA and/or IκB siRNA then exposed to LY294002, the results suggest that the regulatory significantly increased apoptosis in gastric cancer cell. Furthermore, when the cells were pretreated, effect of PI3K/AKT on NF-κB activity is associated with the influence of PI3K/AKT on IKK/IκB. The apoptosis induced by blocking PI3K/AKT might be ascribed to inhibition of NF-κB activity through IKK/IκB at least in part.